TCR-T Cells in the Treatment of Advanced Pancreatic Cancer

To Investigate the Safety, Tolerability, Efficacy and Pharmacokinetics of T Cell Receptor T Cell Therapy in the Treatment of Advanced Pancreatic Cancer

To investigate the safety, tolerability, efficacy and pharmacokinetics of TCR-T cells in the treatment of advanced pancreatic cancer

The aim of this clinical trial is to investigate the safety, tolerability, efficacy and pharmacokinetics of TCR-T cell therapy in patients with advanced pancreatic cancer by intravenous injection, in order to explore an effective cellular immunotherapy method for the treatment of advanced pancreatic cancer

Inclusion Criteria:

• To be eligible for the study, patients must meet all of the following criteria:

  1. Male or female, aged 18-75 years;
  2. Patients with advanced pancreatic cancer diagnosed by histology or cytology, patients who failed to respond to standard treatment, relapsed or voluntarily gave up;
  3. Patients must have tumor tissue that expresses specific tumor antigens, such as mutations in RAS and/or TP53;
  4. Patients must undergo HLA matching testing and meet the requirements of HLA matching.
  5. At least one measurable or evaluable lesion ≥15 mm according to RECIST1.1 criteria;
  6. Patients with ECOG < 2 and life expectancy ≥3 months;
  7. a) Liver function: ALT/AST < 3 times the upper limit of normal value (ULN) and bilirubin ≤34.2μmol/L; b) renal function: creatinine < 220μmol/L; c) terminal oxygen saturation ≥95% in room air; d) Cardiac function: left ventricular ejection fraction (LVEF) ≥60%; e) Blood routine: absolute neutrophil count ≥ 1×109/L; Platelet count ≥70×109/L; Absolute lymphocyte count ≥100 cells /μL;
  8. The patients met the requirements of apheresis without any contraindications.
  9. Women of childbearing age who have a negative urine pregnancy test at screening and before starting dosing and who have agreed to use highly effective contraception for at least 100 days after infusion; Female participants must agree not to donate eggs (oocytes, oocytes) for assisted reproductive purposes during the study and for 90 days after receiving the last study drug;
  10. Male subjects with a fertile partner must consent to use an effective barrier method of contraception for at least 100 days after infusion; Must agree not to donate sperm for at least one year;
  11. Sign an informed consent form.

Exclusion Criteria:

• Patients who met any of the following criteria were not eligible for inclusion in the study:

  1. Persons with severe mental disorders;
  2. A positive virological test for any of the following: HIV; HCV; HBsAg; HBcAb was positive, and HBV DNA copy number and TPPA were positive.
  3. Patients with severe allergic history or allergic constitution;
  4. Severe underlying medical conditions such as evidence of other serious active viral, bacterial or uncontrolled systemic fungal infection; Active autoimmune disease or a history of autoimmune disease within 3 years;
  5. A history of autoimmune diseases (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) leading to end-organ damage or requiring systemic immunosuppressive/systemic disease modulating drugs within the past 2 years;
  6. Combined with organ dysfunction, such as renal insufficiency;
  7. Had been enrolled in another clinical trial within 4 weeks before enrollment in the trial;
  8. Those who were unable to comply with the study protocol and follow-up plan due to physiological, family, social, geographical and other factors;
  9. Patients with contraindications to cyclophosphamide or fludarabine chemotherapy;
  10. Subjects who required additional immunosuppressive drug therapy within 72 hours before TCR-T infusion, except for the treatment of adverse events during the trial;
  11. Pregnant, lactating women, or men who plan to have children while participating in the study or within 100 days of receiving study treatment;
  12. Any other condition considered by the investigator to be ineligible for enrollment.